The proposed project will mainly examine neurochemical responses in mice during withdrawal from chronic administration of alcohol. The neurochemical events to be examined will be those associated with serotonergic and noradrenergic neurotransmission, and those of the adenylate cyclase-cAMP system. The neurochemical changes following cessation of chronic ethanol will be temporally correlated with the onset of withdrawal signs, both behavioral and electroencephalographic. In addition, experimental manipulations will be made so that animals with different withdrawal signs can be produced for neurochemical analyses. The research will also seek further data on the involvement of glucocorticoids in the development of withdrawal syndrome, a finding previously made in our laboratory. The overall aim of the project is to provide information for understanding the neurochemical basis of physical dependence upon alcohol, an important subject for research in experimental alcoholism. It is hoped that such information will contribute to clinical psychiatry in designing effective therapeutic agents for alcoholics.